The role of the complement system of inflammatory proteins in mediating tissue injury in the ischemic myocardium is the objective of the research in progress. A baboon model has been utilized since the baboon and man do not have pre-existing anti-heart autoantibody and baboon complement components are immunochemically and functionally identical with man, thus enabling valuable immunohistochemical probes to be employed. We have shown by ligh immunohistochemistry, using peroxidase-labeled antibodies that C3, C4 and C5 localize in ischemic myocardium within 4 hours after coronary artery ligation. Current investigations will assess the anatomic localization of these and other complement components at the ultrastructural level. Depletion of complement by i.v. administration of purified cobra venom factor significantly reduces myocardial creatine kinase depletion from infarct sites and reduces the number of intermediate or border sites from evolving to infarct within the first 24 hours after ligation. Studies are being conducted to elucidate the mechanisms for such sparing and to determine whether the sparing is more pronounced in the epicardial or endocardial half of the left ventricular muscle.